In recent years, orally disintegrating tablets that rapidly disintegrate in the oral cavity, are being developed as pharmaceutical formulations that can be easily taken by patients with deterioration of swallowing function due to diseases, aging, decrease in saliva production and the like.
In terms of coatings for orally disintegrating tablets, a method in which a coating agent containing a water-soluble polymer is used for an orally disintegrating tablet having not less than a certain degree of hardness, to apply a coating (JP 2010-248106 A), a method in which a coating agent composed of a polyvinyl alcohol derivative and a particular water-soluble substance is used to apply a coating (WO 2010/113841 A1), and a coating containing a particular saccharide and a water-insoluble inorganic compound or water-insoluble fatty acid (WO 2012/147873 A1), have been reported.
On the other hand, most pharmaceuticals are unstable in the presence of oxygen or water vapor, and it is known that, when pharmaceuticals are left to stand in an unpackaged state, certain changes occur in about 40% of the pharmaceuticals, causing serious problems from the viewpoint of their qualities. Thus, most commercially available pharmaceuticals, especially solid preparations, are protected against oxygen and water vapor using a packaging material such as a PTP (press through pack) sheet. In recent years, a PTP sheet having a polyvinylidene chloride laminate, which is excellent in water vapor barrier properties (moisture barrier properties) and oxygen barrier properties, has been developed, and practically used.
As methods of increasing the stability of a solid preparation in the presence of oxygen or water vapor, a method in which the solid preparation is subjected to sugar coating, and a method in which the solid preparation is subjected to film coating using a macromolecular substance, have been practically used.
The sugar coating in the former method is a coating containing sucrose as a main component, and known to have high gas barrier properties and a good external appearance. Examples of such a sugar coating that have been reported so far include a sugar coating agent containing an inorganic macromolecular substance such as montmorillonite (JP 51-57814 A) and a sugar-coated tablet prepared by coating a chewable tablet containing menthol with a sugar coating or sugarless coating (JP 2003-125706 A).
In the latter method by film coating, polyvinyl alcohol and carboxymethyl cellulose are known as macromolecular substances that exert oxygen barrier properties, and aminoalkyl methacrylate copolymer E (EUDRAGIT EPO (registered trademark), manufactured by Degussa) is known as a macromolecular substance that exerts water vapor barrier properties.
Recently, as coatings having increased gas barrier properties, a coating prepared by uniformly dispersing a high hydrogen-bonding resin and a swelling clay in a particular structure (WO 2010/074223 A1), and a coating formed with a coating agent composed of polyethylene glycol and a swelling clay (WO 2012/029820 A1), have also been reported.
However, in solid preparations, rapid disintegration properties and high tablet hardness are opposing properties. Thus, orally disintegrating tablets are insufficient in tablet hardness and high friability. Since, in such tablets, breakage or cracking occurs when they are processed in automatic packaging machines, problems in their handling in the dispensary sites have been pointed out. Moreover, since tablets are stored in the unpackaged state in automatic packaging machines, they are easily affected by storage conditions such as light, temperature, and humidity. Thus, those machines have not been applicable to drugs that are sensitive to the external environment. To solve this, for example, JP 2010-248106 A and WO 2010/113841 A1 describe giving rapid disintegration properties to coatings, and WO 2012/147873 A1 describes improvement of rapid disintegration properties as well as light-blocking properties and moisture barrier properties of coatings. In JP 2010-248106 A and WO 2010/113841 A1, however, although there are descriptions on cracking of the coatings, there is no description on moisture barrier properties of the coatings. Furthermore, in WO 2012/147873 A1, although there is a description on moisture barrier properties, nothing is disclosed about actual measurement values indicating the moisture barrier performance, and there is no description on cracking of the film.
On the other hand, one might think about attempting stabilization by blocking moisture and the like by formation of a coating having gas barrier properties using the coating agent described in WO 2010/074223 A1 or WO 2012/029820 A1. However, when a coating agent to provide gas barrier properties is applied to an orally disintegrating tablet, there is a concern that delay of disintegration due to the coating may occur so that the improvement has been difficult. Moreover, since orally disintegrating tablets are given the rapid disintegration properties by addition of a hygroscopic vehicle and a strong disintegrator, most orally disintegrating tablets increase their volumes under humidified conditions. Therefore, when an orally disintegrating tablet is to be coated, the coating needs to be given strength that is sufficient to withstand swelling of the tablet.
Thus, there is no known coating agent that realizes both rapid disintegration properties and gas barrier properties and, taking the process of water penetration into account, achievement of both properties at the same time has been thought to be difficult.
Furthermore, in coating using a sugar coating as described in JP 51-57814 A and JP 2003-125706 A, the coating is carried out by repeating the steps of liquid pouring, spreading, and drying using a sugar-coating pan. The coating therefore takes a long time, and there are concerns about increases in the sizes of the tablets themselves, and delay of disintegration.
In view of this, it could be helpful to provide a coating agent that imparts gas barrier properties to a solid preparation while keeping rapid disintegration properties of the solid preparation, and a coating formed therewith. It could also be helpful to provide a coated solid preparation that maintains the rapid disintegration properties and gas barrier properties, and does not generate cracks in the coating under humidified conditions.